title: Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: a focus on antidepressant drugs.
abstract: We summarize the alterations of classical neurotransmitters and neuropeptides and the corresponding subreceptors involved in major depression. Neuronal circuits in the brainstem, hippocampus and hypothalamus are developed, since they can be used to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity could occur through a strong presynaptic inhibition of glutaminergic neurons via the subtype 5 of metabotropic glutaminergic receptors, and noradrenaline hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic neurons via GABAB receptors. In the hippocampus, dopamine hypoactivity leads to a decreased positive effect. In clinical trials, the antidepressant effect of drugs interfering with the mentioned subreceptors, for example the triple reuptake inhibitor amitifadine, is being investigated. Moreover, the alterations of neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and galanin are pointed out. The additional antidepressant effect of analogs, agonists and antagonists of the mentioned neuropeptides should be examined.
authors.affiliation: University of Salamanca, Instituto de Neurociencias de Castilla y León (INCYL) Laboratorio de Neuroanatomía de los Sistemas Peptidérgicos (Lab. 14) c/ Pintor Fernando Gallego, 1 37007-Salamanca, Spain. felixm-werner@versanet.de.
authors.forename: Felix-Martin
authors.initials: FM
authors.lastname: Werner
authors.forename: R
authors.initials: R
authors.lastname: Coveñas
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D018079:Receptors, GABA / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D014179:Neurotransmitter Uptake Inhibitors; D018079:Receptors, GABA